6SE3

Crystal Structure of Ancestral Flavin-containing monooxygenase (FMO) 3-6

6SE3 の概要

• エントリーDOI: 10.2210/pdb6se3/pdb
• 分子名称: Ancestral Flavin-containing monooxygenase (FMO) 3-6, FLAVIN-ADENINE DINUCLEOTIDE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: flavin, enzyme, membrane protein, ancestral sequence reconstruction
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 370133.68

構造登録者

Nicoll, C.,Bailleul, G.,Fiorentini, F.,Mascotti, M.L.,Fraaije, M.,Mattevi, A. (登録日: 2019-07-29, 公開日: 2019-12-25, 最終更新日: 2024-01-24)

主引用文献

Nicoll, C.R.,Bailleul, G.,Fiorentini, F.,Mascotti, M.L.,Fraaije, M.W.,Mattevi, A.
Ancestral-sequence reconstruction unveils the structural basis of function in mammalian FMOs.
Nat.Struct.Mol.Biol., 27:14-24, 2020

PubMed Abstract: Flavin-containing monooxygenases (FMOs) are ubiquitous in all domains of life and metabolize a myriad of xenobiotics, including toxins, pesticides and drugs. However, despite their pharmacological importance, structural information remains bereft. To further our understanding behind their biochemistry and diversity, we used ancestral-sequence reconstruction, kinetic and crystallographic techniques to scrutinize three ancient mammalian FMOs: AncFMO2, AncFMO3-6 and AncFMO5. Remarkably, all AncFMOs could be crystallized and were structurally resolved between 2.7- and 3.2-Å resolution. These crystal structures depict the unprecedented topology of mammalian FMOs. Each employs extensive membrane-binding features and intricate substrate-profiling tunnel networks through a conspicuous membrane-adhering insertion. Furthermore, a glutamate-histidine switch is speculated to induce the distinctive Baeyer-Villiger oxidation activity of FMO5. The AncFMOs exhibited catalysis akin to human FMOs and, with sequence identities between 82% and 92%, represent excellent models. Our study demonstrates the power of ancestral-sequence reconstruction as a strategy for the crystallization of proteins.

PubMed: 31873300
DOI: 10.1038/s41594-019-0347-2

実験手法

X-RAY DIFFRACTION (2.8 Å)